There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units...

Descriptions of time use patterns in people with chronic obstructive pulmonary disease (COPD) are scarce and the relationship between use-of-time and COPD severity remains unclear. This study aimed to describe a typical day for people with COPD and to explore the differences in time-use patterns across the Body Mass-Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) index using compositional analyses. Using a cross-sectional design, 141 adults with clinically stable COPD had their demographics, objective measures of function (pulmonary, exercise capacity and physical activity), and self-reported COPD-related impairment recorded...

PURPOSE OF REVIEW: Successful roll-out of paediatric antiretroviral therapy (ART) has led to a significant increase in survival of adolescents and young people growing up with HIV. Those on suppressive ART since childhood represent a unique group particularly well positioned to interrupt ART and achieve post-treatment control (PTC), or HIV remission. This maybe a consequence of early and sustained treatment since infancy, the small size of the HIV reservoir, the presence of a functioning thymus and a more 'flexible' immune system better able to respond to novel immune therapeutic interventions when compared with adults who acquired HIV at a time of immunological maturity and thymic involution...

Yeast-two-hybrid (Y2H) cDNA library screening is a valuable tool to uncover protein-protein interactions and represents a widely used method to investigate protein function. However, cDNA libraries with low transcript representation limits the depth of the screening. We have developed a Y2H library with cDNA made from Arabidopsis leaves exposed to several stressors as well as untreated leaves. The library was built using pooled mRNA extracted from plants challenged with plant and human bacterial pathogens, the flg22 elicitor, the phytotoxin coronatine, and several hormones associated with environmental stress responses...

Screening against a disease-relevant phenotype to identify compounds that change the outcome of biological pathways, rather than just the activity of specific targets, offers an alternative approach to find modulators of disease characteristics. However, in pain research, use of in vitro phenotypic screens has been impeded by the challenge of sourcing relevant neuronal cell types in sufficient quantity and developing functional end-point measurements with a direct disease link. To overcome these hurdles, we have generated human induced pluripotent stem cell (hiPSC)-derived sensory neurons at a robust production scale using the concept of cryopreserved "near-assay-ready" cells to decouple complex cell production from assay development and screening...

Background: Due to the paucity of quick, cognitive screening tools available in India that are independent of cultural and educational influences, a 6-item paper and pencil test, covering areas of memory, executive functioning, attention, and visuospatial ability domains - the Neuropsychological Evaluation Screening Tool (NEST) was developed. Aim and Method: NEST was administered to 84 healthy controls to analyze, revise, and review items. In the second phase, 408 patients, above 16 years of age, with their educational level ranging from being illiterate to having greater than 25 years of education, with various neurological and psychiatric conditions were independently administered NEST, Hindi Mental State Examination (HMSE), and a detailed cognitive evaluation using PGI Memory Scale (PGIMS)...

INTRODUCTION: Preferential viewing of novel stimuli in the Visual Paired Comparison task has provided a useful marker of memory and medial temporal lobe function. We created a portable version of the VPC (P-VPC) and contrasted P-VPC metrics against the Montreal Cognitive Assessment (MoCA) in healthy adults, to assess the validity and reliability of the P-VPC as an indicator of memory function across age. A supplementary case series was conducted with individuals diagnosed with Alzheimer's disease (AD) and other dementias, to provide a preliminary illustration of the P-VPC's use as a measure in clinical populations...

Schwannomas are benign nerve tumors that occur sporadically in the general population and in those with neurofibromatosis type 2 (NF2), a tumor predisposition genetic disorder. NF2-associated schwannomas and most sporadic schwannomas are caused by inactivating mutations in Schwann cells in the neurofibromatosis type 2 gene (NF2) that encodes the merlin tumor suppressor. Despite their benign nature, schwannomas and especially vestibular schwannomas cause considerable morbidity. The primary available therapies are surgery or radiosurgery which usually lead to loss of function of the compromised nerve...

The purpose of this study was to assess outcome measures and cost-effectiveness of robotic colorectal resections in adult patients with inflammatory bowel disease. The Cochrane Library, PubMed/Medline and Embase databases were reviewed, using the text "robotic(s)" AND ("inflammatory bowel disease" OR "Crohn's" OR "Ulcerative Colitis"). Two investigators screened abstracts for eligibility. All English language full-text articles were reviewed for specified outcomes. Data were presented in a summarised and aggregate form, since the lack of higher-level evidence studies precluded meta-analysis...

The interaction and organization of proteins in the sperm membrane are important for all aspects of sperm function. We have determined the interactions between twelve known mutationally defined and cloned sperm membrane proteins in a model system for reproduction, the nematode Caenorhabditis elegans. Identification of the interactions between sperm membrane proteins will improve our understanding of and ability to characterize defects in sperm function. To identify interacting proteins, we conducted a split-ubiquitin membrane yeast two-hybrid (MYTH) analysis of gene products identified through genetic screens that are necessary for sperm function and predicted to encode transmembrane proteins...

Objective: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The identification of new simple, inexpensive and highly accurate markers for HCC diagnosis and screening is needed. This case-control study evaluates the role of annexin A2 and voltage-gated calcium channels α2δ1 subunit as serum biomarkers for HCC diagnosis. Methods: The study comprised three groups: group 1, 50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection; group 2, 25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC; and group 3, 15 healthy controls...

Rescoring is a simple approach that theoretically could improve the original docking results. In this study AutoDock Vina was used as a docked engine and three other scoring functions besides the original scoring function, Vina, as well as their combinations as consensus scoring functions were employed to explore the effect of rescoring on virtual screenings that had been done on diverse targets. Rescoring by DrugScore produces the most number of cases with significant changes in screening power. Thus, the DrugScore results were used to build a simple model based on two binding site descriptors that could predict possible improvement by DrugScore rescoring...

The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation...

Soluble amyloid β oligomers (AβOs) are widely recognized neurotoxins that trigger aberrant signaling in specific subsets of neurons, leading to accumulated neuronal damage and memory disorders in Alzheimer's disease (AD). One of the profound downstream consequences of AβO-triggered events is dysregulation of cytosolic calcium concentration ([Ca2+ ]i ), which has been implicated in synaptic failure, cytoskeletal abnormalities, and eventually neuronal death. We have developed an in vitro/in vivo drug screening assay to evaluate putative AβO-blocking candidates by measuring AβO-induced real-time changes in [Ca2+ ]i ...

Breast cancer (BC) is a leading cause of death in women worldwide. Active mutations of PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification of its homolog PIK3CB occur in many BC cases. In recent years, activation of the Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have been found to be important for BC development and progression. However, there is no evidence that PI3K interacts with YAP/TAZ in mammary tumorigenesis. Using a systematic gain-of-function screen for kinases involved in mammary tumorigenesis, PIK3CB was identified as a transformation inducing kinase...

<u>Rationale:</u> Atherosclerosis is a chronic inflammatory disease that is driven by the interplay of pro- and anti-inflammatory leukocytes in the aorta. Yet, the phenotypic and transcriptional diversity of aortic leukocytes is only poorly understood. <u>Objective:</u> We characterized leukocytes from healthy and atherosclerotic mouse aortas in-depth by single cell RNA-sequencing (scRNAseq) and mass cytometry (CyTOF) to define an atlas of the immune cell landscape in atherosclerosis...

In vitro-grown megakaryocytes for generating platelets may have value in meeting the increasing demand for platelet transfusions. Remaining challenges have included the poor yield and quality of in vitro-generated platelets. We have shown that infusing megakaryocytes leads to intrapulmonary release of functional platelets. A Src kinase inhibitor (SU6656), a Rho-associated kinase inhibitor (Y27632), and an aurora B kinase inhibitor (AZD1152) have been shown to increase megakaryocyte ploidy and in vitro proplatelet release...

Until recently, spina bifida has been regarded a pediatric health issue, and adult consequences of the disorder have not been explored. The congenital neurologic and urologic anomalies, as well as sequelae of bladder management, can have a profound impact on adult male sexual function. Abnormalities in testicular descent, testicular development and function, fertility, penile sensation, erectile function, ejaculatory function, and orgasmic function are common in this population. These adults have substantial gaps in knowledge in normal sexual function and potential dysfunction as it relates to them specifically...

High throughput screens for developmental neurotoxicity (DN) will facilitate evaluation of chemicals and can be used to prioritize those designated for follow-up. DN is evaluated under different guidelines. Those for drugs generally include peri- and postnatal studies and juvenile toxicity studies. For pesticides and commercial chemicals, when triggered, include developmental neurotoxicity studies (DNT) and extended one-generation reproductive toxicity studies. Raffaele et al. (2010) reviewed 69 pesticide DNT studies and found two of the four behavioral tests underperformed...

BACKGROUND AND OBJECTIVE: Early-stage diagnosis of laryngeal cancer is of primary importance to reduce patient morbidity. Narrow-band imaging (NBI) endoscopy is commonly used for screening purposes, reducing the risks linked to a biopsy but at the cost of some drawbacks, such as large amount of data to review to make the diagnosis. The purpose of this paper is to present a strategy to perform automatic selection of informative endoscopic video frames, which can reduce the amount of data to process and potentially increase diagnosis performance...